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    Regenerative cell therapy, tissue engineering are future treatments

    While ALK, EK have evolved for corneal replacement, researchers seeking new directions

     

    Tissue engineering

    For tissue engineering, there are two systems that are close to human trials. One in Japan is already in human clinical trials, and the Singapore center has applied for an IRB clinical trial for their full GMP compliant system.

    They take repurposed corneas that would otherwise be thrown away due to low endothelial cells, and expand the cell number. The idea is to generate enough cells to expand this at a high cellular density. Using this protocol, which has been published in Cell Transplantation4, 90 constructs can be made with about 3,000 cells/mm2 density.

    The cells then need to be delivered, and there are two ways of doing this. One method is anterior chamber injection cell therapy, and the other is putting them on to a carrier. There are advantages and disadvantages to both systems.

    Injection cell therapy is simple and is undergoing human trials. However, there can be inconsistency in the density. The cells can go all over the anterior chamber, and there is some variability in the outcomes reported in the literature.

    If a ROCK inhibitor is used, it must be put in at the time, and there is not a clinical grade one approved. If the patient has Fuchs’, what is to be done with the guttata? There needs to be a Descemet’s membrane there intact for the cells to stick, so should the guttata be removed or left in place?

    When using a construct, the cell density can be better controlled and it is more reproducible in the delivery. However if you use a synthetic carrier, this must undergo GMP approval.

    Tissue that is thrown away will be repurposed for tissue engineering.

    EK techniques can be improved using the CAM system. The strategy for treating Fuchs’ dystrophy will vary.

    For mild-to-moderate cases, it will be a Descemet’s membrane transplant with or without ROCK inhibitor, depending on age. More severe cases will require an endothelial approach so the guttata can be removed.

    For bullous keratotomy, cell injection will work well, though advanced cases might need tissue engineered construct. For regraft cases, cell injection works because there is a basement membrane there for the cells to attach. Regulatory authorities will present some limitations to the widespread use of all these concepts.

     


    Reference

    1. Coster DJ, Lowe MT, Keane MC, Williams KA; Australian Corneal Graft Registry Contributors. A comparison of lamellar and penetrating keratoplasty outcomes: a registry study. Ophthalmology. 2014 May;121(5):979-87.

    2. Akanda ZZ, Naeem A, Russell E, Belrose J, Si FF, Hodge WG. Graft rejection rate and graft failure rate of penetrating keratoplasty (PKP) vs lamellar procedures: a systematic review. PLoS One. 2015 Mar 17;10(3):e0119934. doi: 10.1371/journal.pone.0119934. eCollection 2015 Mar 17. Review.

    3. Rizwan M, Peh GS, Adnan K, Naso SL, Mendez AR, Mehta JS, Yim EK. In Vitro Topographical Model of Fuchs Dystrophy for Evaluation of Corneal Endothelial Cell Monolayer Formation. Adv Healthc Mater. 2016 Nov;5(22):2896-2910. doi: 10.1002/adhm.201600848. Epub 2016 Oct 4.

    4. Peh GS, Chng Z, Ang HP, Cheng TY, Adnan K, Seah XY, George BL, Toh KP, Tan DT, Yam GH, Colman A, Mehta JS. Propagation of human corneal endothelial cells: a novel dual media approach. Cell Transplant. 2015;24(2):287-304. doi: 10.3727/096368913X675719. Epub 2013 Nov

     

    Jodhbir Mehta, PhD

    E: jodmehta@gmail.com

    Dr. Mehta did not have any financial disclosures in regard to the content of this article.

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